The objective of this investigation is to establish "force-duration" diagrams of various types of sickle cells (S-rbc) undergoing morphological change and intracellular molecular aggregation. Quantitative observation of time-dependent (duration) changes of sickle cell under different partial pressures (force) of oxygen will be carried out using the rbc-monolayer system developed by the principal investigator. Under conditions when the oxygenation level of S-rbc is being changed, the kinetics of transport of oxygen through rbc will be measured. Any change in the kinetics in S-rbc is the reflection of intracellular physical change as well as of cell status. The conditions to be studied are representative of the duration of time circulating rbc spend in tissue capillaries and the expected partial pressure of oxygen at these sites. One cell or a group of cells can be studied in this system, both spectrophotometrically and visually. The "force-duration" diagrams will be examined in relation to the age and historical condition of S-rbc, to intracellular constituents--inclusive of genetic variants of S-rbc and to the irreversibly sickled S-rbc. The effects of drugs on the "force-duration" diagram will reveal more quantitative understanding of effectiveness of these drugs with regard to dissociating aggregates or preventing their formation within the time that cells are exposed to different partial pressures of oxygen.